The rich chemistry of the carbon-iodine bond has made it a particularly rewarding synthetic tool of routine use for the purpose of functional group interconversion. Organic iodides are valuable and versatile intermediates in the synthesis of functional materials and biologically active compounds such as medical drugs and agricultural chemicals. In particular, alkyl and aryl iodides serve as excellent substrates for transition metal-catalyzed homo- and cross-coupling reactions, which are used for the synthesis of complex molecules. As the iodine atom is an excellent leaving group, iodosubstituted organic compounds have been recognized as valuable synthons or precursors in organic synthesis, above all in carbon-carbon, carbon-nitrogen, carbon-oxygen or carbon-sulfur bond formation.
Thus, various organic iodides have been produced commercially and have been used in laboratory and industrial synthesis. For example, 1-Boc-4-iodomethylpiperidine is the starting material for the synthesis of donepezil and icopezil and 1-Boc-4-iodopiperidine is used for the synthesis of 4-arylpiperidine moiety, which is a structural feature which can be found in a wide variety of active pharmacologic agents. The iodides also find use as intermediates in the preparation of other compounds, especially zinc organic compounds. Nucleophilic displacement reactions of the iodides yield sulfonic acid esters, nitro derivatives and mercaptans.
Aromatic iodides possess a much higher reactivity than other aromatic halides in Ullmann condensation reactions. Typically, aryl iodides have higher kinetic rates of product formation than other aromatic halides, as illustrated by the reduced reaction times necessary to produce higher yields of highly pure products than with other aromatic halides. Thus, aryl iodides are key substrates in the Ullmann condensation reactions traditionally used to manufacture charge transporting and hole transporting triarylamine compounds (U.S. Pat. No. 7,138,555).
Nucleophilic iodination of organic hydroxy, chloro, and bromo derivatives is usually used for the formation of organic iodides. For example, 1-Boc-4-iodopiperidine and 1-Boc-4-iodomethylpiperidine were prepared from related hydroxy-derivatives by reaction with iodine and triphenylphosphine. The disadvantages of such reactions include difficulties in separation and utilization of triphenylphosphine oxide as main by-product of the reactions.
Carboxylic acids are widely available and cheap raw materials in the organic synthesis, so the oxidative decarboxylation of carboxylic acids with concomitant replacement by iodine (iodo-de-carboxylation) comprises an extremely useful procedure for the syntheses of organic iodides. The unreacted acid may be easily recovered by treatment of the iodo-de-carboxylation reaction mixture with aqueous base and then acid. This makes the reaction also attractive for iodo-de-carboxylation of acids with low reactivity.
The Hunsdiecker reaction (Johnson, Chem. Rev. 1956, v. 56, 219) includes an iodo-de-carboxylation reaction, by treatment of anhydrous silver salt of the acid with iodine in an inert solvent. However, the reaction is extremely sensitive to trace amounts of water, the presence of which leads to the recovery of unreacted acid. Unfortunately, the preparation of dry silver salts of carboxylic acids is difficult and, such salts are usually quite sensitive to heat also, they are often quite hard to dry thoroughly. Another way to perform the Hunsdiecker reaction is by use of a mixture of the acid and I2/HgO (Cristol & Firth, J. Org. Chem. 1961, v. 26, 280) or I2/Pb(OAc)4 (Barton et al., J. Chem. Soc., 1965, 2438) instead of the silver salt. Accordingly, the Hunsdiecker reaction and/or its modifications use heavy metal salts such as those of silver, mercury and lead and the disadvantages of such procedures for pharmaceutical industry are obvious.
The Barton iodo-de-carboxylation procedure (Barton et al., Tetrahedron 1985, v. 41, 3901 and Tetrahedron, 1987, v. 43, 4321) includes conversion of carboxylic acids to the esters of N-hydroxypyridine-2-thione. The thiohydroxamic esters are iodinated by CHI3, and CH2I2 in cyclohexene solution. Thiopyridines are formed in the reaction as significant by-products.
Another method for the conversion of R—COOH to R—I includes reacting carboxylic acids with iodine and dibenzoyl peroxide. High concentration of peroxide in the reaction mixture may promote explosive. Iodobenzene is formed in the reaction as a significant by-product.
Additional process for converting carboxylic acids to their corresponding iodides is by treating the carboxylic acid with (diacetoxyiodo)benzene (DIB) and iodine under irradiation conditions (Suarez et al., J. Org. Chem. 1986, v. 51, 402 and Boto et al., Eur. J. Org. Chem. 2005, 673); wherein iodobenzene was formed in the reaction as significant by-product.
Barton used tert-butyl hypoiodite in a Hunsdieker type reaction to iodo-decarboxylate carboxylic acids. tert-Butyl hypoiodite is not commercially available reagent, has low thermal stability of the reagent and should be used immediately after preparation. Therefore, tert-butyl hypoiodite cannot be used for the preparation of aryl-iodide compounds.
N-iodo amides such as N-iodosuccinimide (NIS), N-iodosaccharine (NISac), 1,3-diiodo-5,5-dimethylhydantoin (DIH), triiodoisocyanuric acid (TICA) (Tetrahedron Letters 2007, v. 48, 8747), 2,4,6,8-tetraiodoglycoluril (TIG) (Tetrahedron Letters 2000, v. 41, 9101) etc., are used as efficient reagents for the electrophilic iodination of organic compounds.

However, the use of these reagents as source of iodine for reactions of iodo-de-carboxylation are limited. Reaction of N-halosuccinimides with aryl acrylic and aryl propiolic acids gives 1-halo-2-aryl-1-alkenes and 1-halo-2-aryl-1-alkynes (J. Org. Chem. 2002, v. 67, 7861; J. Org. Chem. 1999, v. 64, 6896; J. Org. Chem. 1997, v. 62, 199; Tetrahedron 2000, v. 56, 1369). All the reactions occur in the presence of catalyst. Reaction of α-(cyclopropylsulfonyl)phenylacetic acid with NIS gives α-iodobenzyl cyclopropyl sulfone only with 32% yield (J. Org. Chem. 1974, v. 39, 2516).